The aim of this research program involves elucidation of the ion conductances expressed by cells cultured from the embryonic CNS and from primary and clonal endocrine cells. Specific lines of investigation include projects on the embryonic development, cellular distribution and functional roles of the conductances in membrane excitability. Electrical measurements of ion conductance activities either at the microscopic level in membrane patches or at the whole-cell level with the patch-clamps technique and with single- and double-microelectrode penetrations are strongly influenced by the assay method itself. Thus, although the different assay techniques are all quite useful and provide complementary data for characterizing the membrane mechanisms underlying ion conductances in these cells, there are advantages and disadvantages to the application of each. Principal observations to date include the following: l) electrically excitable membrane properties develop early, well before birth as soon as cells can be studied; 2) although a number of cation and anion conductances have been characterized in a relatively quantitative manner, none appear unique to the vertebrate or to the cell studied; and 3) the conductances underlie specific patterns of excitability, which serve to transform, in a still ill-defined way, synthetic events in the cytoplasm into defined secretory activities. Particular attention has been given to those mechanisms most commonly expressed and to identifying those exhibited by specific cell types (e.g., motoneurons, GABAergic cells). It appears that certain, relatively ubiquitous mechanisms have similar electrical properties in phenotypically distinct types of cultured neurons. Pharmacological experiments involving anti-glycine-receptor antibodies have revealed that certain immunoreagents can mimic agonist actions. Such a line of investigation will allow us to examine the roles played by different subunits in the generation of an electrical response on the post-synaptic membrane by glycine. This strategy is undoubtedly generalizable to immunoreagents specific for other transmitter receptor/ion channel complexes.